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Notch‐inducing hydrogels reveal a perivascular switch of mesenchymal stem cell fate


Blache, Ulrich; Vallmajo‐Martin, Queralt; Horton, Edward R; Guerrero, Julien; Djonov, Valentin; Scherberich, Arnaud; Erler, Janine T; Martin, Ivan; Snedeker, Jess G; Milleret, Vincent; Ehrbar, Martin (2018). Notch‐inducing hydrogels reveal a perivascular switch of mesenchymal stem cell fate. EMBO Reports, 19(8):e45964.

Abstract

The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production. We demonstrate that the ECM phenotypic switch of MSCs can be recapitulated in the absence of endothelial cells by functionalizing PEG hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs in Notch-inducing microenvironments reveals the reversibility of this ECM switch. These findings provide insight into the perivascular commitment of MSCs by use of engineered niche-mimicking synthetic hydrogels.

Abstract

The fate of mesenchymal stem cells (MSCs) in the perivascular niche, as well as factors controlling their fate, is poorly understood. Here, we study MSCs in the perivascular microenvironment of endothelial capillaries by modifying a synthetic 3D biomimetic poly(ethylene glycol) (PEG)-hydrogel system in vitro We show that MSCs together with endothelial cells form micro-capillary networks specifically in soft PEG hydrogels. Transcriptome analysis of human MSCs isolated from engineered capillaries shows a prominent switch in extracellular matrix (ECM) production. We demonstrate that the ECM phenotypic switch of MSCs can be recapitulated in the absence of endothelial cells by functionalizing PEG hydrogels with the Notch-activator Jagged1. Moreover, transient culture of MSCs in Notch-inducing microenvironments reveals the reversibility of this ECM switch. These findings provide insight into the perivascular commitment of MSCs by use of engineered niche-mimicking synthetic hydrogels.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Obstetrics
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Genetics, Biochemistry, Molecular Biology
Language:English
Date:1 August 2018
Deposited On:07 Dec 2018 06:45
Last Modified:24 Sep 2019 23:55
Publisher:Nature Publishing Group
ISSN:1469-221X
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.15252/embr.201845964
PubMed ID:29967223
Project Information:
  • : FunderFP7
  • : Grant ID607868
  • : Project TitleITERM - Training scientists to develop and Image materials for Tissue Engineering and Regenerative Medicine

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